Contraction and Relaxation Flashcards

(37 cards)

1
Q

what channels allow the entry of Ca into the cardio myocyte

A

RyR2

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2
Q

where does intracellular Ca get released from?

A

Sarcoplasmic reticulum

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3
Q

where does the Ca bind to

A

troponin C on actin filaments in the sarcomere

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4
Q

how does the heart muscle relax?

A

K channels open

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5
Q

what receptor takes the Ca back into the sarcoplasmic reticulum

A

SERCA2a

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6
Q

what receptor removes Ca from the cell

A

NXC (Na+/Ca2+ exchanger)

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7
Q

how many ryanodine receptor isotypes are there?

A

3

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8
Q

which isotype is found in the heart

A

RyR2

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9
Q

how are RyR2 receptors arranged?

A

clusters

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10
Q

what does activation of the RyR2 clusters cause

A

calcium spark

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11
Q

what can lead to leaky RyRs

A

caffeine

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12
Q

where/what are RyRs

A

Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca2+ from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle

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13
Q

consequence of a leaky RyR

A

calcium escape from the intracellular stores into the cytosol possibly causing a premature atrial contraction

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14
Q

effect of low [caffeine]

A

increased sensitivity to RyRs to cytosolic Ca2+

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15
Q

What is SERCA2a

A

SERCA is a type P ATPase pump that transports two calcium ions in exchange of the hydrolysis of one ATP molecule, functioning against a calcium gradient to restore luminal ER calcium levels

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16
Q

what activates SERCA2a

A

increased cytosolic Ca

17
Q

what regulates SERCA2a

18
Q

How can PLN activate SERCA2a

A

if high [Ca] AND PLN is phosphorylated itself (on CAMK11 and PKA sites)

19
Q

what is NCX

A

Na/Ca exchanger

20
Q

what drives the NCX

A

increased cytosolic [Na] or [Ca]

21
Q

how can this operate

A

forward or reverse

22
Q

which is the normal direction?

A

forward (Ca x 1 out, Na x 3 in)

23
Q

what activates the forward direction of the NCX

A

increased cytosolic Ca

24
Q

what is an adverse side effect of NCX

A

can cause membrane depolarisation, which triggers DADs in Ca2+ overloaded myocytes

25
how does the forward reaction affect the cytosolic [Ca]
decreases it
26
how is Ca2+ homeostasis regulated in the cardiac myocyte
sympathetic nervous system
27
4 main phosphorylation sites
Cav1.2 (calcium channel) RyR2 (on SP) Troponin 1 PLN-mediated SERCA
28
PLN-mediated SERCA can also cause an
increase in force contraction
29
EADs can be caused by
hyperphosphorylation and enhanced activity of Cav1.2
30
what predominant effect do catecholamines have
positive inotropic
31
how do catecholamines have a positive inotropic effect
increase [Ca] in the cytosol via PKA mediated phosphorylation of L-VACC and Ca release via RyR2
32
how do catecholamines have a negative inotropic effect
increase Ca reuptake into the SR via PKA-mediated phosphorylation of SERCA (the PLB becomes phosphorylated)
33
4 examples of catecholamines that have a positive inotropic effect
NA, A, dobutamine, isoprenaline
34
what effect does digoxin have
inhibit Na/K ATPase
35
effect of digoxin
- binds to extracellular K+ site competitively, inactivating it, - increasing [Na] in the cytoplasm - REVERSE mode on NCX - more Ca into the cell - +ve inotropy
36
over dose of digoxin
- increased Ca in cytoplasm - stimulate FORWARD NCX - NCX is electrogenic, so more +ve charges enter than exit - membrane depolarisation - DADs --> arrhythmias
37
levosimendan
is a +ve inotrope